As pharmaceuticals which act on the circulatory system, many products are known to date, including a variety of products developed as vasodilators.
Among such vasodilators, .alpha..sub.1 -blockers led by prazosin are the targets of active developments, because they have advantages such that (1) their antihypertensive action is strong and reliable, (2) they do not adversely affect lipometabolism or saccharometabolism and (3) they can be used easily for hypertensives suffering from complication. As .alpha..sub.1 -blockers which are currently in clinical use, bunazosin, terazosin, urapidil, doxazosin and the like can be mentioned in addition to prazosin. Further, medicines having .alpha..sub.1 -blocking action and anti-serotonin action in combination are expected to become still better therapeutics for hypertension, because they have possibility to reduce side effects, such as orthostatic hypotension and reflex tachycardia, induced by antihypertensive action which is based on .alpha..sub.1 -blocking action.
Further, a hypertensive is considered to be prone to an ischemic heart disease or peripheral circulatory disturbance, since his or her platelet aggregating ability has been generally potentiated to have higher thrombophilia. As one of those taking part in thrombosis, serotonin is known. Serotonin is a compound contained abundantly in platelets, which are a blood component, and in a central nervous system, on the other hand, it acts as a neurotransmitter. In platelets, it is released upon stimulation by thromboxane A.sub.2, ADP, collagen or the like, and synergistically acts on release of various platelet aggregation factors through activation of serotonin-2 receptors in the platelets and vascular smooth muscle cells and also on vasoconstriction by norepinephrine through .alpha..sub.1 receptors, thereby inducing strong platelet aggregation and vasoconstriction [P.M. Vanhoutte, "Journal of Cardiovascular Pharmacology", Vol. 17 (Suppl. 5), S6-S12 (1991)].
Serotonin is also known to potentiate proliferation of vascular smooth muscle cells [S. Araki et al., "Atherosclerosis", Vol. 83, pp.29-34(1990)]. It has been considered that, particularly when endothelial cells are injured as in arteriosclerosis or myocardial infarction, the vasoconstricting action and thrombus forming action of serotonin are exasperated, thereby reducing or even stopping blood supply to myocardial, cerebral and peripheral organs [P. Golino et al., "The New England Journal of Medicine", Vol. 324, No. 10, pp.641-648(1991), Y. Takiguchi et al., "Thrombosis and Haemostasis", Vol. 68(4), pp.460-463(1992), A. S. Weyrich et al., "American Journal of Physiology", Vol. 263, H349-H358(1992)]. Being attracted by such actions of serotonin or serotonin-2 receptors, various attempts are now under way to use a serotonin-2 receptor antagonist as a pharmaceutical for ischemic diseases of the heart, the brain and peripheral tissues.
From the foregoing, a medicine having .alpha..sub.1 -blocking action and serotonin-2 receptor antagonistic action in combination is expected to have vasodilative action, antiplatelet action and vascular smooth muscle proliferation inhibiting action, and is considered to become a medicine extremely effective for the prevention or treatment of not only hypertension but also general circulatory diseases such as heart failure, ischemic heart diseases such as angina pectoris, myocardial infarction and post-PTCA restenosis, cerebrovascular disturbances such as cerebral infarction and cerebral sequelae after subarachnoid hemorrhage, and peripheral circulatory disturbances such as arteriosclerosis obliterans, thromboangiitis obliterans, Raynaud disease and Buerger disease.
Until today, several medicines have been reported to have .alpha..sub.1 -blocking action and serotonin-2 receptor antagonistic action in combination. They are however still accompanied with many problems to be improved in potency, selectivity to other receptors, toxicity, side effects and the like. There is hence an outstanding desire for the provision of a still better compound.